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Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis

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World Journal of Gastroenterology 2017年第29期23卷 5412-5421页

作者： Tamas Tornai Eszter Palyu Zsuzsanna Vitalis Istvan Tornai David Tornai Peter Antal-Szalmas Gary L Norman Zakera Shums Gabor Veres Antal Dezsofi Gabriella par alajos par Peter Orosz Ferenc Szalay Peter Laszlo Lakatos Maria Papp Institute of Internal Medicine Department of Gastroenterology University of Debrecen Faculty of Medicine Department of Laboratory Medicine University of Debrecen Faculty of Medicine Debrecen Inova Diagnostics Inc.San Diego 1^st Department of Pediatrics Semmelweis University 1^st Department of Medicine University of Pecs Gastroenterology Department of Medicine Borsod-Abauj Zemplen County Hospital 1^st Department of Medicine Semmelweis University

AIM To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis(PSC) *** Sera of 67 PSC patients [median age(range): 32(5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin(AAA Ig A/Ig G) and gliadin(AGA Ig A/Ig G)] and for serum level of intestinal fatty acid-binding protein(I-FABP) by ELISA. Markers of lipopolysaccharide(LPS) exposure [LPS binding protein(LBP)] and various antimicrobial antibodies [anti-OMP Plus Ig A and endotoxin core Ig A antibody(Endo CAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99(14-106) mo]. One hundred and fifty-three healthy subjects(HCONT) and 172 ulcerative colitis(UC) patients were the controls. RESULTS A total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA Ig A, AAA Ig G, AGA Ig A and AGA Ig G, respectively. Frequencies of AAA Ig A and AAA Ig G(P pared to both of the HCONT and the UC groups. In survival analysis, AAA Ig A-positivity was revealed as an independent predictor of poor disease outcome after adjusting either for the presence of cirrhosis [HR = 5.15(1.27-20.86), P = 0.022 or for the Mayo risk score(HR = 4.24(0.99-18.21), P = 0.052]. AAA Ig A-positivity was significantly associated with higher frequency of antimicrobial antibodies(P < 0.001 for Endo Cab Ig A and P = 0.012 for anti-OMP Plus Ig A) and higher level of the enterocyte damage marker(median I-FABP_(AAA Ig A pos vs neg): 365 vs 166 pg/m L, P = 0.011), but not with serum LBP level. CONCLUSION Presence of Ig A type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various microbial antigens and e

关键词：主要 sclerosing 胆管炎毁坏障碍机能障碍肠的丰满的酸绑定的蛋白质 Anti-F-actin 抗体反麦胶蛋白质抗体

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Immunological changes in different patient populations with chronic hepatitis C virus infection

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World Journal of Gastroenterology 2016年第20期22卷 4848-4859页

作者： Laszlo Szereday Matyas Meggyes Melinda Halasz Julia Szekeres-Bartho alajos par Gabriella par Department of Medical Microbiology and Immunology University of PecsClinical Centre7624 PecsHungary Janos Szentagothai Research Centre 7624 PecsHungary First Department of Internal Medicine University of PecsClinical Centre7624 PecsHungary

AIM: To investigate killer inhibitory and activating receptor expression by natural killer(NK), natural killer T-like(NKT-like) and CD8+ T lymphocytes in patients with chronic hepatitis C virus(HCV) infection with elevated and with persistently normal alanine aminotransferase(PNALT).METHODS: The percentage of peripheral blood Treg cells, KIR2DL3, ILT-2, KIR3DL1, CD160, NKG2 D, NKG2 C expressing NK, T and NKT-like cells, cytokine production and NK cytotoxicity were determined by flow cytometry. Twenty-one patients with chronic HCV infection with elevated alanine aminotransferase, 11 HCV carriers with persistently normal alanine aminotransferase and 15 healthy volunteers were enrolled. RESULTS: No significant differences were observed in the percentage of total T, NK or NKT-like cells between study groups. Comparing the activating and inhibitoryreceptor expression by NK cells obtained from HCV carriers with PNALT and chronic HCV hepatitis patients with elevated alanine aminotransferase, NKG2 D activating receptor expression was the only receptor showing a significant difference. NKG2 D expression of NK cells was significantly lower in patients with elevated alanine aminotransferase. The expression of CD160, NKG2 D and NKG2 C activating receptor by CD8+ T cells were significantly lower in patients with chronic HCV hepatitis than in healthy controls and in HCV carriers with PNALT. Plasma TGF-β1 levels inversely correlated with NKG2 D expression by NK cells. In vitro TGF-β1 treatment inhibited NK cells cytotoxic activity and downregulated NKG2 D expression. CD8+ T cells from HCV carriers with PNALT showed significantly elevated expression of CD160, NKG2 D and NKG2 C activating receptors compared to chronic HCV patients with elevated alanine aminotransferase. Enhanced expression of inhibitory KIR2DL3 receptor, and decreased ILT-2 expression on NK cells were also found in chronic hepatitis C patients compared to healthy ***: Our study demonstrated a complex

关键词： Hepatitis C Natural killer cell NKG2D Cytotoxicity Cytokine

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